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Development 129, 681-693 (2002)
© 2002 The Company of Biologists Limited

Dual origin of spinal oligodendrocyte progenitors and evidence for the cooperative role of Olig2 and Nkx2.2 in the control of oligodendrocyte differentiation

Hui Fu1,*, Yingchuan Qi1,*, Min Tan1,*, Jun Cai1, Hirohide Takebayashi2, Masato Nakafuku3, William Richardson4 and Mengsheng Qiu1,{dagger}

1 Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, KY 40292, USA
2 Department of Pathology and Tumor Biology Graduate School of Medicine, Kyoto University Konoe-chou, Sakyo-ku, Kyoto 606-8501, Japan
3 Department of Neurobiology, University of Tokyo, Graduate School of Medicine, 7-3-1 Hongo, Bunkyoku, Tokyo 113-0033, Japan
4 Wolfson Institute for Biomedical Research, The Cruciform Building, University College London,Gower Street, London WC1E 6AE, UK
* These authors contributed equally to this work

{dagger}Author for correspondence (e-mail: m0qiu001{at}louisville.edu)

Accepted 1 November 2001

In this study, we have investigated the relationship of Olig2+ and Nkx2.2+ oligodendrocyte progenitors (OLPs) by comparing the expression of Olig2 and Nkx2.2 in embryonic chicken and mouse spinal cords before and during the stages of oligodendrogenesis. At the stages of neurogenesis, Olig2 and Nkx2.2 are expressed in adjacent non-overlapping domains of ventral neuroepithelium. During oligodendrogenesis stages, these two domains generate distinct populations of OLPs. From the Olig2+ motoneuron precursor domain (pMN) arise the Olig2+/Pdgfra+ OLPs, whereas the Nkx2.2+ p3 domain give rise to Nkx2.2+ OLPs. Despite their distinct origins, both populations of OLPs eventually appear to co-express Olig2 and Nkx2.2 in the same cells. However, there is a species difference in the timing of acquiring Nkx2.2 expression by the Olig2+/Pdgfra+ OLPs. The co-expression of Nkx2.2 and Olig2 in OLPs is tightly associated with myelin gene expression in the normal and PDGFA–/– embryos, suggesting a cooperative role of these transcription factors in the control of oligodendrocyte differentiation. In support of this suggestion, inhibition of expression of these two transcription factors in culture by antisense oligonucleotides has an additive inhibitory effect on OLP differentiation and proteolipid protein (PLP) gene expression.

Key words: Oligodendrocyte progenitors, Embryonic origins, Nkx2.2, Olig2, Expression, Pdgfa mutant, Antisense inhibition


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© The Company of Biologists Ltd 2002